tbuckley/cabot-search huggingface dataset:
First-line PD-1 inhibitors immunotherapy and chemotherapy combined with or without radiotherapy for patients with advanced non-small cell lung cancer.
Authors: Peng Ding, Yu Huang, Fan Tong, Lingjuan Chen, Lu Wen, Ruiguang Zhang, Shishi Cheng, Xiaorong Dong
Journal: Journal of Clinical Oncology (2022)

2606 Background: Immunochemotherapy has become a standard first-line regimen for advanced non-small-cell lung cancer (NSCLC). Several studies showed the synergistic effects of immunotherapy and radiotherapy on local and abscopal tumour control. But the data of first-line immunochemotherapy combined with radiotherapy for the advanced NSCLC is still scarce. Methods: Patients with advanced NSCLC receiving first-line PD-1 inhibitors immunotherapy plus chemotherapy in a single center were retrospectively analyzed in this study. They were divided into two groups according to whether they had received radiotherapy. The efficacy and safety of first-line immunochemotherapy combined with radiotherapy (ICRT group) and immunochemotherapy alone (ICT group) were investigated. Results: A total of 135 patients were included; 65 patients received PD-1 inhibitors plus chemotherapy and radiotherapy, while other 70 patients were treated with immunochemotherapy alone. The median interval time between radiotherapy and PD-1 inhibitors immunotherapy was 5 days (range, 0-96 days). The overall response rate (ORR) was 50.8% in the ICRT group and 40.0% in the ICT group, respectively. Patients in the ICRT group achieved significant longer progression-free survival (PFS, median 16.5 vs 10.4 months, P= 0.043) and overall survival (OS, median not reached vs 21.0 months, P= 0.030) compared with those in the ICT group. The addition of radiotherapy was the only prognostic factor for PFS (HR = 0.617, 95%CI: 0.385-0.989, P= 0.045) and OS (HR = 0.512, 95%CI: 0.277-0.947, P= 0.033) by univariate Cox regression analysis. Patients were well tolerated and the overall incidence of adverse events was similar between the ICRT group and ICT group. One patient in ICRT group stopped immunotherapy because of severe immune-associated pneumonia. 3.1% of grade 3-4 radiation-related adverse events were observed. Conclusions: Adding radiotherapy to first-line PD-1 inhibitors immunotherapy and chemotherapy improved outcomes of patients with advanced NSCLC and showed acceptable toxicity. Additional prospective studies exploring the first-line combination of immunochemotherapy and radiotherapy are warranted.
The drug targets genomic alterations detected in female tumor tissue with melanoma.
Authors: Zhongwu Li, Xintong Wang
Journal: Journal of Clinical Oncology (2022)

e21558 Background: Due to the rapid development of next-generation sequencing (NGS) and precision medicine, molecularly driven targeted therapy, for different tumor types, plays an important role in cancer patients with drug targets. mucosal melanoma (MM) is aggressive disease with a poor prognosis. there are few studies focusing on its target drug. Methods: We enrolled female patients with melanoma (n = 24) from 2019.** to 2021.** cancer database with a gynecological tumor site. Subsequently, we chose to use WES sequencing to predict possible targets in patients. Results: In all mutations of the 24 melanoma patients, we screen the mutations about the drug targets. And the result shown that BRAF somatic mutations were identified in 6 of the 24 samples (25%), which are the highest frequency drug targets. V600E substitutions accounted for 3 (50%) of these mutations as target drug. Other activating mutations at NRAS codons 61 and 12/13 were lower frequent (Q61*, n = 3; G13D, n = 1; G12A, n = 1). TP53 and TOP2B were mutated in 4(16%) tumors were found as drug targets. Conclusions: This study aimed to analyze the target drug interaction of MM in China and lay a support for targeted therapy. NGS in MM is feasible with potential impact in half of our cohort. Earlier testing and improved trial drug from drug bank database access is necessary to increase the like hood that MM patients may benefit from drug target guided therapy.
Lisocabtagene maraleucel (liso-cel) as second-line (2L) therapy for R/R large B-cell lymphoma (LBCL) in patients (pt) not intended for hematopoietic stem cell transplantation (HSCT): Primary analysis from the phase 2 PILOT study.
Authors: Alison Sehgal, Daanish Hoda, Peter A. Riedell, Nilanjan Ghosh, Mehdi Hamadani, Gerhard Hildebrandt, John E. Godwin, Patrick Michael Reagan, Nina D. Wagner-Johnston, James Essell, Rajneesh Nath, Scott R. Solomon, Rebecca Champion, Edward Licitra, Suzanne Fanning, Neel K. Gupta, Ronald L. Dubowy, Aleco D’Andrea, Lei Wang, Leo I. Gordon
Journal: Journal of Clinical Oncology (2022)

7062 Background: Pts with R/R LBCL after first-line (1L) treatment (tx) who are unable to undergo high-dose chemotherapy (HDCT) and HSCT have poor outcomes and limited tx options. PILOT (NCT03483103) evaluated liso-cel, an autologous, CD19-directed chimeric antigen receptor (CAR) T cell product, as 2L tx in pts with R/R LBCL not intended for HSCT. Methods: Eligible pts were adults with R/R LBCL after 1L tx who were not deemed candidates for HDCT and HSCT by their physician and met ≥ 1 frailty criteria: age ≥ 70 yr, ECOG PS = 2, DLCO ≤ 60%, LVEF &lt; 50%, CrCl &lt; 60 mL/min, or ALT/AST &gt; 2 × ULN. Bridging tx was allowed. Pts received lymphodepletion with cyclophosphamide and fludarabine, followed 2–7 days later by liso-cel at a target dose of 100 × 10 6 CAR + T cells. Cytokine release syndrome (CRS) was graded per Lee 2014 criteria and neurological events (NE) per NCI CTCAE, version 4.03. Primary endpoint was ORR per independent review committee (IRC); all pts had ≥ 6 mo follow-up (f/u) from first response. Results: Of 74 pts leukapheresed, 61 received liso-cel and 1 received nonconforming product. Common reasons for pre-infusion dropout included death and loss of eligibility (5 each). For liso-cel–treated pts, median age was 74 yr (range, 53–84; 79% ≥ 70 yr) and 69%, 26%, and 5% met 1, 2, and 3 frailty criteria, respectively; 26% had ECOG PS = 2 and 44% had HCT-CI score ≥ 3. After 1L tx, 54% were chemotherapy refractory, 21% relapsed ≤ 12 mo, and 25% relapsed &gt; 12 mo; 51% of pts received bridging chemotherapy. Median (range) on-study f/u was 12.3 mo (1.2–26.5). ORR and CR rate was 80% and 54%, respectively. Median DOR and PFS was 12.1 mo and 9.0 mo, respectively. Median OS has not been reached (Table). Most frequent tx-emergent AEs (TEAE) were neutropenia (51%), fatigue (39%), and CRS (38%), with grade (gr) 3 CRS in 1 pt (2%) and no gr 4/5 CRS. Any-grade NEs were seen in 31%, gr 3 in 5% (n = 3), and no gr 4/5 NEs; 7% received tocilizumab, 3% corticosteroids, and 20% both for tx of CRS/NEs. Overall, gr ≥ 3 TEAEs occurred in 79%, with gr 5 in 2 pts (both due to COVID-19). Two pts (3%) had gr 3/4 infections and 15 (25%) had gr ≥3 neutropenia at Day 29. Conclusions: In the PILOT study, liso-cel as 2L tx in pts with LBCL who met ≥ 1 frailty criteria and for whom HSCT was not intended demonstrated substantial and durable overall and complete responses, with no new safety concerns. Clinical trial information: NCT03483103. [Table: see text]
Outcomes in patients undergoing curative surgery for gastric cancer by facility type and socioeconomic factors: An analysis of the National Cancer Database (NCDB).
Authors: Ali Alqahtani, Kaitlyn Dykes, Chao Yin, Xue Geng, Hongkun Wang, Benjamin Adam Weinberg
Journal: Journal of Clinical Oncology (2022)

4066 Background: Surgical and medical treatment for resectable gastric cancer is complex, and multidisciplinary team involvement is essential to provide optimal treatment outcomes. However, socioeconomic disparities influence the quality of medical care patients receive. We hypothesized that facility type, median income, insurance type, and location would impact patients' overall survival (OS). Methods: In a retrospective analysis of NCDB data, we identified patients with stage II and III gastric adenocarcinoma who underwent curative-intent surgical resection and chemotherapy between 2004-2018. Demographic and socioeconomic factors were studied, including treatment facility type, median household income, urban/rural residence, and insurance status. Multivariate Cox proportional hazard model was used to evaluate the impact of these variables on overall survival (OS). The Kaplan-Meier method was used to estimate OS. Log-rank test was used to compare the OS between groups. Results: Based on the criteria listed above, 36,318 patients were identified: 76.3% were Caucasian, 14.4% black, 7.2% Asian, and 2.0% other. 56.4% lived in large metropolitan areas (LM), 29.9% in small/medium metropolitan areas (SM), and 14.2% in rural areas (RA). Patients who were treated in academic/research programs had significantly better OS (mOS 40.5 months) compared to integrated-network cancer programs (mOS 34.0 months, HR 0.897, p &lt; 0.0001), comprehensive community cancer programs (mOS 31.0 months, HR 0.89, p &lt; 0.0001), and community cancer programs (mOS 29.5, HR 0.881, p &lt; 0.0001). Patients from LM had better OS compared to those from SM and RA (mOS 39.0, 32.1, 29.9 months respectively, p &lt; 0.0001). Privately insured patients had improved OS compared to Medicare-insured patients (mOS 40.8 vs 29.7 months, HR 0.758, p &lt; 0.0001). Higher annual income (≥ $63,000) was positively associated with improved OS (p &lt; 0.0001). Conclusions: Outcomes for patients with gastric cancer treated with surgery and chemotherapy are strongly influenced by socioeconomic variables, including place of residence, treatment setting, insurance, and income level. We highlight improved outcomes in patients who resided in LM and were treated at academic/research centers. A potential hypothesis for this trend is increased access to specialized, multidisciplinary care and clinical trials.
Trifluridine/tipiracil plus bevacizumab (FTD/TPI + BEV) and trifluridine/tipiracil (FTD/TPI) monotherapy in metastatic colorectal cancer (mCRC): Results of a meta-analysis.
Authors: Takayuki Yoshino, Julien Taieb, Thierry Andre, Yasutoshi Kuboki, Per Pfeiffer, Amit Kumar, Howard S. Hochster
Journal: Journal of Clinical Oncology (2022)

3568 Background: FTD/TPI is approved for patients (pts) with refractory mCRC. FTD/TPI + BEV has been evaluated in refractory mCRC in phase 1 and 2 trials and shown efficacy and tolerability, but few head-to-head studies compare FTD/TPI + BEV with FTD/TPI. We therefore conducted this meta-analysis to evaluate outcomes with FTD/TPI + BEV and FTD/TPI monotherapy in mCRC. Methods: We searched MEDLINE, Embase, and Cochrane Library databases; ASCO, ESMO, and AACR proceedings (past 3 years); Clinicaltrials.gov and UMIN registries; systematic review bibliographies; gray literature; and guidelines through June 2021 for studies involving pts with mCRC treated with FTD/TPI + BEV or FTD/TPI. Only randomized controlled trials (RCTs), non-RCTs, and prospective observational studies of previously treated pts with mCRC were evaluated. Outcomes included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), adverse event (AE) rates, and AE-related discontinuation rates. Fixed and random effects models based on inverse-variance weighting were used to estimate relative effects and pooled absolute outcomes for ORR, DCR, AE rates, and AE-related discontinuation rates. PFS and OS were estimated from pooled Kaplan–Meier curves using Guyot’s algorithm. Results: Twenty-nine of 875 screened publications were selected, which included a total of 10,285 pts and reported on 5 RCTs, 11 non-RCTs, and 10 prospective observational studies. In an RCT (n = 93; Pfeiffer et al. Lancet Oncol. 2020), FTD/TPI + BEV was associated with significant reductions in risks for progression and death versus FTD/TPI. Pooled efficacy outcomes were higher with FTD/TPI + BEV than FTD/TPI (Table). Pooled rates for grade ≥3 febrile neutropenia, asthenia/fatigue, diarrhea, nausea, and vomiting were similar with FTD/TPI + BEV and FTD/TPI, although grade ≥3 neutropenia occurred more frequently with FTD/TPI + BEV than FTD/TPI (43% vs 29%). AE-related discontinuation rates were similar (Table). Conclusions: This meta-analysis suggests that FTD/TPI + BEV provides benefits over FTD/TPI in pts with refractory mCRC and has a similar safety profile, but it is associated with a higher rate of grade ≥3 neutropenia. Limitations of the analysis include study design heterogeneity. Data from RCTs (eg, phase 3 SUNLIGHT trial [NCT04737187]) are required to confirm these findings. [Table: see text]
Impact of preauthorization review on oncology drug and radiation costs.
Authors: James Austin Talcott, Megan Salmon-Gardell, Vlad Kozlovsky, Erik Yedwab, Traci Boehringer, Tiffany P. Avery
Journal: Journal of Clinical Oncology (2022)

e18829 Background: Preauthorization review (PR) is designed to ensure that patients receive evidence-based medicine (EBM) treatment but also affects costs. We estimated changes in chemotherapy and radiation costs when PR found treatments to deviate from EBM. Methods: We identified chemotherapy and radiation treatment plans reviewed by Eviti Connect in 2020 found to contain medically unjustified deviations from EBM after a request for peer-to-peer discussion. We calculated the cost difference in antineoplastic and supportive drugs and radiation procedures between deviating plans and any approved replacements. We assumed completion of curative drug regimens and 4 months duration for non-curative treatments. Results: We report net change in treatment costs for all patients with plans reviewed. Of 13,370 patients with reviewed plans, 1-4 deviating plans were identified for 1899 patients (14.2%), or 2160 deviating plans. Mean savings were $38,242 (95%CI $35,354 - $41,118) per patient with a deviating plan, $33,097 (95%CI $30,851- $35,343) per deviating plan, and $5,348 per patient with a plan reviewed. Inflation-adjusted per patient savings were 27% greater than we reported in 2012. Total savings were $71,497,374. Applying these results to a covered population of 1 million, assuming 0.3% undergo PR annually, would save $16,041,000. Provider appeals were submitted for 2.2% of cases found deviating and 0.3% were upheld. Conclusions: PR directly ensures EBM cancer care by identifying deviating treatments and reduces treatment costs. This analysis likely underestimates realized savings because it includes only drug and radiation procedure costs; noncurative treatments often extend beyond 4 months; and provider experience with PR may deter submitting treatments previously determined to be deviating.
Mebendazole in recurrent glioblastoma: Results of a phase 2 randomized study.
Authors: Nandini Sharrel Menon, Abhishek Chatterjee, Raees Tonse, Amit Choudhary, Abhishek Mahajan, Ameya Puranik, Epari Sridhar, Shruti Pathak, Monica Jadhav, Zoya Peelay, Rutuja Walavalkar, Hemanth Kumar, Madala Ravi Krishna, Arun Chandrasekharan, Nikhil Pande, Tejpal Gupta, Shripad Dinanath Banavali, Rakesh Jalali, Vijay Maruti Patil
Journal: Journal of Clinical Oncology (2022)

2029 Background: Recurrent glioblastoma (GBM) has dismal outcomes and limited treatment options. Mebendazole (MBZ) is an anti-helminthic drug with in-vivo and in-vitro activity against glioma cell lines and has been demonstrated to be well tolerated in combination with lomustine (CCNU) and temozolomide (TMZ). In this phase 2 study, we sought to determine whether the addition of MBZ to CCNU or TMZ would improve overall survival (OS) in recurrent GBM. Methods: Adult patients with ECOG PS 0-3, with recurrent glioblastoma who were not eligible for re-radiation, were randomized 1:1 between CCNU-MBZ (n = 44) and TMZ-MBZ (n = 44). The primary endpoint was OS at 9 months, selected to reflect the BELOB trial. A 9-month OS of 55% or more in any arm was hypothesized to warrant further evaluation and a value below 35% was too low to warrant further investigation. Results: At 17.4 months, 68 events for OS analysis had occurred. The 9-month overall survival was 36.6% (95%CI 22.3-51) and 45% (95%CI 29.6-59.2) in the TMZ-MBZ and CCNU-MBZ arms respectively. ECOG PS was the only independent prognostic factor impacting OS (HR-0.478 95%CI 0.268-0.851; P = 0.012). Twenty-three patients (28.6%) enrolled had an ECOG PS 2-3 with inferior outcomes (median OS-5.67, HR-2.092 95%CI 1.175-3.731). Analysis restricted to ECOG PS 0-1 (n = 65) patients revealed a 9-month OS of 39.6% (95% CI 22.4-56.3) and 57.9% (95% CI 38.7-73) in TMZ-MBZ and CCNU-MBZ arms respectively. Grade 3-5 adverse events were seen in 8 (18.6%; n = 43) and 4 (9.5%; n = 42) patients in the TMZ-MBZ and CCNU-MBZ arms respectively. Conclusions: The addition of MBZ to TMZ or CCNU failed to achieve the pre-set benchmark of 55% 9-month OS. This was probably due to 28.6% of patients with poor PS of 2-3. In patients with ECOG PS 0-1, CCNU-MBZ had a 9 month OS of 57.9% and needs to be evaluated further. Clinical trial information: CTRI/2018/01/011542.
Real-world progression-free and overall survival for patients with advanced ovarian cancer utilizing PARP inhibitor second-line maintenance therapy vs active surveillance.
Authors: Robert Lawrence Reid, Junxin Shi, Alisha Monnette, Katrine L Wallace
Journal: Journal of Clinical Oncology (2022)

e18812 Background: Ovarian cancer (OC) is the fifth leading cause of cancer death among women. Poly(ADP-ribose) polymerase inhibitors (PARPis) are recommended following response to second-line (2L) chemotherapy as 2L maintenance treatment by the National Comprehensive Cancer Network for OC patients (pts), based on results from clinical trials demonstrating their ability to extend progression-free survival (PFS), the time between chemotherapy and relapse, in this patient population. We present recent estimates of real-world PFS and overall survival (OS) for pts on 2L PARPi maintenance therapy vs active surveillance. Methods: From the iKnowMed electronic health record database and a review of patient charts within the US Oncology Network, which includes 1200 physicians operating in over 470 sites of care in the US, adult females were included if they were diagnosed with advanced OC, had received a 2L platinum-containing regimen for advanced OC, and had ≥2 visits within the database between 1 Jan 2016 and 1 Dec 2020. Among these, a subset of charts were reviewed to confirm eligibility and to assess PFS. Patients were followed longitudinally until 31 March 2021, the last pt record, or date of death, whichever occurred earliest. Kaplan-Meier survival methods and log-rank tests were used to estimate and compare the OS as well as PFS of the groups to 24 months. Results: A total of 1154 pts met study inclusion criteria for advanced OC and either a PARPi or active surveillance for the 2L maintenance period. Of these, 142 patient charts were further manually reviewed to assess real-world PFS: 84 received a PARPi, and 58 received active surveillance. Median age at the start of 2L maintenance was 65.7 years and was not significantly different between groups. There was a significant difference in the distribution of the ECOG PS category between groups (ECOG PS 0: 22.6% vs 1.7%, ECOG PS 1: 39.3% vs 50.0%, for PARPi vs active surveillance, respectively; P&lt; 0.0001). Median follow-up time from discontinuation of 2L platinum chemotherapy until the end of observation was significantly longer in the active surveillance group (41.5 vs 23.5 months; P&lt; 0.0001). PFS probability from the beginning of 2L maintenance was higher in the PARPi group vs active surveillance (24% vs 10% at 24 months; P= 0.0003). OS probability was also significantly higher in the PARPi group vs active surveillance (78% vs 55% at 24 months; P= 0.0272). Conclusions: This study of PARPi therapy vs active surveillance confirms the efficacy benefits that have been demonstrated in randomized clinical trials of PARPis vs placebo, and it provides further evidence of the real-world effectiveness of PARPi maintenance therapy to improve survival in a population with advanced OC.
Molecular disease monitoring in patients with relapsed/refractory B-cell non-Hodgkin lymphoma receiving anti-CD19 CAR T-cell therapy.
Authors: Meryl D. Colton, Enkhtsetseg Purev, Bradley Haverkos, Steven Michael Bair, Jagar Jasem, Mark Jason Schliekelman, Manali K. Kamdar
Journal: Journal of Clinical Oncology (2022)

7531 Background: Chimeric antigen receptor (CAR) T-cell therapy has improved the historically poor outcomes for relapsed and refractory (R/R) B-cell non-Hodgkin’s lymphoma (NHL). However, nearly 60% of patients will either fail to respond or relapse after CAR T-cell therapy. Currently, PET/CT scans are used to assess response. Cell-free circulating tumor DNA (ctDNA) is released by tumor cells into the peripheral blood and can be measured for minimal residual disease (MRD) assessment. Methods: In this retrospective, IRB approved pilot study, archived lymphoma tissues and ctDNA from peripheral blood samples on day 0, 14, 28, 56, 80, 180, and 365 after CAR T-cell infusion from 10 patients with R/R NHL were collected for next-generation sequencing (NGS) of clonal variable-diversity-joining (VDJ) rearrangements [Adaptive biotechnologies (Seattle, WA)]. Response was assessed by PET/CT on days 30, 60, 90, 180 and 365 and graded according to the Lugano 2014 criteria. The primary endpoint was to determine the feasibility of detecting ctDNA to monitor disease response after anti-CD19 CAR T-cells. The secondary endpoint was to compare the sensitivity/specificity of MRD assessment from ctDNA to PET/CT imaging. Results: Nine out of 10 patients with a trackable sequence [median age 69 (range: 56-76); 55.6% male; median LDH 224], were included in this study. Each received tisagenlecleucel CAR T-cell therapy after median two prior treatments (range: 2-4). 7/9 patients had R/R diffuse large B-cell lymphoma (DLBCL), and 2/9 had transformed follicular lymphoma. At a median follow up of 12.7 months (range: 1.5-30 months), four patients were alive. By day 90, three patients (33.3%) achieved a radiographic complete response (CR) whilst six patients (66.6%) had progressive disease (PD). MRD and radiographic response are outlined in the Table. Detectable MRD on day 14 or day 28 had 83% sensitivity and 100% specificity for radiographic progression at any time before one year. For patients with PD, the median (interquartile range) MRD at day 0, 14, and 28 were 17.31 (1.01, 96.84), 9.12 (0.30, 18.8), and 23.77 (8.01, 137.53) copies per milliliter (mL), respectively. For patients with detectable MRD at day 28, mOS and mPFS were 205 and 38 days, respectively. Conclusions: Our pilot study demonstrated that monitoring MRD was a sensitive and specific method to detect disease response and relapse. In addition, MRD can be monitored more frequently, thus allowing for earlier detection of relapse. MRD and PET/CT identified progressive disease (PD) or complete response (CR) by day 90 in nine patients (A-I) with R/R NHL post CAR T-cell infusion.[Table: see text]